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Journal of Antimicrobial Chemotherapy (1994) 33, 273-279
© 1994 The British Society for Antimicrobial Chemotherapy

research-article

Bioavailability and chemotherapeutic activity of clofazimine against Mycobacterium avium complex infections in beige mice following a single implant of a biodegradable polymer

Subramanian Kailasam1, Donald L. Wise1 and Pattisapu R. J. Gangadharam2,

1 Mycobacteriology Research Laboratories, Section of Infectious Diseases, University of Illinois College of Medicine at Chicago Chicago, IL 60612 2 Chemical Engineering Department, Northeastern University Boston, MA 02115, USA

Received 16 February 1993; accepted 22 September 1993

Dr P. R. J. Gangadharam. Mycobacteriology Research, University of Illinois, College of Medicine, 835 S. Wolcott, Room E709, Chicago, IL 60612, USA.

We have studied the bioavailability of clofazimine following administration of a single dose of the drug in the biodegradable polymer polylactic-co-glycolic acid (PLGA). We compared the levels of clofazimine achieved in the liver with single implants with those obtained with daily oral treatment. Even though the levels achieved with implants were much lower than those obtained after daily oral treatment, they were higher than the MIC of clofazimine for Mycobacterium leprae, Mycobacterium tuberculosis and Mycobacterium avium complex (MAC). Experimental studies in beige mice after infection with MAC strain 101 showed similar reductions in cfu counts, after both single dose polymer and daily oral treatment. Macroscopically, hyperpigmentation giving an orange-yellow colour to all visceral organs, was seen in animals after daily oral treatment but not in those animals that received polymer implants.


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